Targeting secretion to the apical surface by mDia1-built actin tracks

The apical surface of secretory tubular epithelia is a dynamic cellular domain where massive membrane turnover takes place during exocytosis and its subsequent compensatory endocytosis. This extensive membrane flow poses a difficulty in targeting secretory vesicles efficiently to a narrow apical domain. We have studied how actin filaments mediate the secretory process in the murine exocrine pancreas, which produces and secretes digestive enzymes that are deposited into the intestine. We show that cargo-filled secretory vesicles move over bundles of linear actin cables from their storage areas to the apical membrane of pancreatic acinar cells. mDia1, a linear actin nucleator of the Formin family, was identified as the generator of these structures. The active form of mDia1 localizes to the apical surface, and the microfilament bundles it forms emanate from the apical surface and extend into the cytoplasm, generating polarized secretion tracks. These bundles ensure orderly progression of exocytosis, since the apical targeting of pancreatic vesicles is compromised in their absence, and vesicles fuse with each other to generate compound, membrane-associated secretory structures.